With painter Virgil Williams and photographer Carleton Watkins, Hill made his first trip to the Yosemite Valley in 1865. The next year, Hill traveled to the East Coast and Europe. He established his family on the East Coast but continued to take sketching trips to the West Coast and to attend meetings of the San Francisco Art Association. He moved his family back to San Francisco in 1873.

Hill made yearly sketching trips to Yosemite, Mount Shasta, and, back east, to the White Mountains. Hill ran an art gallery and art supply store. He briefly acted as the interim director for the SFAA School of Design and went to Alaska on a commission for environmentalist John Muir. He lived on his stock market investments as well as his art proceeds. His marriage ended in the 1880s.

Hill’s work was often driven by a vision resulting from his experiences with nature. For Thomas Hill, Yosemite Valley and the White Mountains of New Hampshire were his sources of inspiration to begin painting and captured his direct response to nature.[2]

Hill was loosely associated with the Hudson River School of painters. The Hudson River School celebrated nature with a sense of awe for its natural resources, which brought them a feeling of enthusiasm when thinking of the potential it held. Mainly the earlier members of the Hudson River School, around the 1850-60’s, displayed man as in unison with nature in their landscape paintings by often painting men on a very small scale compared to the vast landscape. Thomas Hill often brought this technique into his own paintings in for example in his painting, Yosemite Valley 1889.

He made early trips to the White Mountains with his friend Benjamin Champney and painted White Mountain subjects throughout his career. An example of his White Mountain subjects is Mount Lafayette in Winter. Hill acquired the technique of painting en plein air. These paintings in the field later served as the basis for larger finished works.

In plein air means to “paint outdoors and directly from the landscape”,[3] which Hill incorporated into many of his paintings. Hill’s landscape paintings demonstrate how he combined his powers of observation with powerful motifs in each painting.

Hill’s move to California in 1861 brought him new material for his paintings. He chose monumental vistas, like Yosemite. During his lifetime, Hill’s paintings were popular in California, costing as much as $10,000. Hill's best works are considered to be these monumental subjects, including Great Canyon of the Sierra, Yosemite, Vernal Falls and Yosemite Valley.

His 1865 View of the Yosemite Valley was chosen to be the backdrop of the head table at Barack Obama's inaugural luncheon, to commemorate Lincoln's 1864 signing of the Yosemite Grant. A painting has been chosen for every inaugural luncheon since 1985.[4]